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Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins

Nature Cell Biology volume 4, pages 639–647 (2002)Cite this article

Abstract

The Rho family GTPases Rac, Rho and Cdc42 are critical in regulating the actin-based cytoskeleton, cell migration, growth, survival and gene expression. These GTPases are activated by guanine nucleotide-exchange factors (GEFs). A biochemical search for Cdc42 activators led to the cloning of zizimin1, a new protein whose overexpression induces Cdc42 activation. Sequence comparison combined with mutational analysis identified a new domain, which we named CZH2, that mediates direct interaction with Cdc42. CZH2-containing proteins constitute a new superfamily that includes the so-called 'CDM' proteins that bind to and activate Rac. Together, the results suggest that CZH2 is a new GEF domain for the Rho family of proteins.

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Figure 1: Specific binding of zizimin1 to nucleotide-depleted Cdc42.
Figure 2: Expression and function of zizimin1.
Figure 3: Filopodia induction by zizimin1.
Figure 4: Sequence of zizimin1.
Figure 5: Structure of zizimin1 and its homologues.
Figure 6: The zizimin1 CZH2 domain is necessary and sufficient for Cdc42 binding.
Figure 7: Binding and activation of Cdc42 by the C2H2 domain.

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Acknowledgements

We thank T. Nagase from the Kazusa DNA Research Institute for providing the KIAA1058 cDNA. We thank C. Der for providing Dbl expressing NIH-3T3 cells and R. Cerione for the D118A Cdc42. We are grateful to J. Han for advice about GEF assays and to N. Alderson for excellent technical assistance. This work was supported by grants from the U.S. Public Health Service (RO1 GM41721) to M.A.S., grants from the American Heart Association to N.M. and W.B.K. and from the Leukemia & Lymphoma society to M.A.P.

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  1. Division of Vascular Biology, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Nahum Meller, Mohammad Irani-Tehrani, William B. Kiosses, Miguel A. Del Pozo & Martin A. Schwartz

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  1. Nahum Meller
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Correspondence to Martin A. Schwartz.

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Figure S1. Gel analysis of immunoprecipitates. (PDF 124 kb)

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Meller, N., Irani-Tehrani, M., Kiosses, W. et al. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nat Cell Biol 4, 639–647 (2002). https://doi.org/10.1038/ncb835

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